Dichloromethane → HCID 66731831, compound

HRID 1963180Notes

Reaction equation

HRID 1963180 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][C:20]=1[F:34].C(Cl)Cl>CO.Cl[Pd]Cl.O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:21][C:20]=1[F:34]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 222401464-Chloro-3-fluorophenylboronic acid pinacol ester

Product 1

HCID 66731831HCID 66731831, compoundYield 79.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (1.2 g, 6.99 mmol), potassium carbonate (0.580 g, 4.20 mmol) and PdCl2 (dppf) (0.122 g, 0.17 mmol) were combined in a microwave vial. 2-(4-Chloro-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.1 g, 8.19 mmol) dissolved in MeOH (15 mL) was added. The reaction mixture was heated in a single node microwave reactor at 100° C. for 15 min. DCM (125 mL) and water (125 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (125 mL). The combined organic phases were washed with brine (250 mL), dried with a phase separator and evaporated in vacuo. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column. A gradient of 10% EtOAc in heptane over 3 CV and then 10 to 50% EtOAc in heptane over 12 CV was used as mobile phase. The product was collected using the wavelength 253 nm. Methyl 2-(4-chloro-3-fluorophenyl)isonicotinate (1.473 g, 79%) was isolated as a white solid. 1H NMR (400 MHz, cdcl3) δ 4.00 (s, 3H), 7.48-7.54 (m, 1H), 7.76-7.83 (m, 2H), 7.88-7.94 (m, 1H), 8.24-8.27 (m, 1H), 8.83 (dd, 1H).

Workup

  1. additionwas added
  2. customthe phases separated
  3. extractionThe aqueous phase was extracted with DCM (125 mL)
  4. washThe combined organic phases were washed with brine (250 mL)
  5. customdried with a phase separator
  6. customevaporated in vacuo
  7. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column
  8. customThe product was collected

Sources & evidence

ORD record
ord-1bd3ae02c224450b95ff3c2cddce821b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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